Development of early diagnostic method using Alzheimer's disease model mice

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07829
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Health Sciences University of Hokkaido
• Principal Investigator: FUJII Hirotada 北海道医療大学, その他, 客員教授 (70209013)
• Co-Investigator(Kenkyū-buntansha): 下濱 俊 札幌医科大学, 医学部, 名誉教授 (60235687)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: アルツハイマー病 / 酸化ストレス / レドックス / EPRイメージング

Outline of Final Research Achievements

Alzheimer's disease (AD) is the most common neurodegenerative disease causing progressive cognitive decline. One of the histopathological hallmarks of AD is aggregated amyloid-β (Aβ) proteins. In addition to the typical pathological changes of AD, oxidative stress is also reported to be an important pathological phenomenon that starts to manifest early in the course of AD. Oxidative stress induced by the generation of reactive oxygen species (ROS) is a prominent phenomenon in AD and is known to occur early in its course. In the present study, we developed a newly designed digital electron paramagnetic resonance (EPR) imager with redox-sensitive piperidine nitroxide probe for early detection of changed brain redox status. Using this system, the obtained brain redox images of AD and control mice clearly showed impaired brain redox status of AD mice compared to control, and this change was apparently seen in 7-month-old AD mice compared with age-matched control mice.

Free Research Field

磁気共鳴

Academic Significance and Societal Importance of the Research Achievements

本研究課題では、ADモデルマウスの脳内レドックス状態を非侵襲で可視化しうる、電子常磁性共鳴法(EPR)を用いたAD病態の早期診断システムを開発した。本研究で開発したシステムを用いると、ADモデルマウスの脳内にアミロイドβタンパク質が蓄積し始める9ヶ月例よりも早い6～7ヶ月齢で脳内酸化ストレス状態が変化することを検出することが出来た。　この研究手法を活用すると、ADモデルマウスにどのような介入をすることでいち早く脳内レドックス状態の変動が起こりうるかを予測することが出来、ADの始まりの状態である軽度認知障害（MCI）への移行を早期に発見でき、AD患者増加の抑制に貢献することが出来る。